Impact of inoculum size and heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) on vancomycin activity and emergence of VISA in an in vitro pharmacodynamic model.

The activity of vancomycin against heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) and non-hVISA isolates, using an in vitro pharmacodynamic model, was reduced in the presence of a high inoculum amount (10(8) CFU/ml). A high bacterial load of >10(5) CFU/ml persisted for all strains with doses up to 5 g every 12 h against high inoculum amounts. No change in the vancomycin MIC was detected in any isolate at a moderate inoculum amount (10(6) CFU/ml), and bactericidal activity occurred only against the non-hVISA isolate (time to 99% kill, 7.5 h; P = 0.001).

Occurrence of vancomycin-tolerant and heterogeneous vancomycin-intermediate strains (hVISA) among Staphylococcus aureus causing bloodstream infections in nine USA hospitals.

BACKGROUND: The bactericidal activities of vancomycin and daptomycin were evaluated in a large collection of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia strains from nine major USA medical centres. OBJECTIVES: To evaluate the occurrence of heterogeneous vancomycin-intermediate S. aureus (hVISA) among MRSA strains tolerant to vancomycin and/or with increased vancomycin or daptomycin MIC values. The accuracy of the macro Etest method (MET) compared with population analysis profiling (PAP) for the detection of hVISA was also assessed. METHODS: A total of 1800 MRSA strains were collected from bloodstream infections at the nine sites (40 strains per year, per medical centre during the 2002-06 study period). Vancomycin and daptomycin MIC testing was performed by reference broth microdilution (all strains) and MBC tests on 50% of strains (randomly selected). A subset of isolates (n = 268) having an increased vancomycin MBC (> or =16 mg/L), an increased vancomycin MIC (> or =1 mg/L) and/or an increased daptomycin MIC (>0.5 mg/L) were tested for susceptibility to vancomycin and teicoplanin by MET. RESULTS: Overall, 181 of 900 (20.1%) MRSA tested exhibited vancomycin tolerance, varying from 10% to 43% among the medical centres evaluated, and from 11.7% in 2004 to 27.8% in 2005. No resistance trend was observed in any medical centre or in the overall study data. Daptomycin showed bactericidal activity against all strains tested. The accuracy of MET for identifying hVISA strains varied significantly with the criteria applied for positivity. CONCLUSIONS: The most frequently used criteria to define hVISA, i.e. MET reading values > or =8 mg/L for both vancomycin and teicoplanin or > or =12 mg/L for teicoplanin only, detected 20 of 36 PAP-positive strains (55.6% sensitivity), indicating that the prevalence of hVISA could be higher than currently appreciated. Daptomycin was bactericidal against hVISA strains.

Evaluation of the Etest GRD for the detection of Staphylococcus aureus with reduced susceptibility to glycopeptides.

OBJECTIVES: Continued glycopeptide-selective pressure has led to non-susceptible strains of Staphylococcus aureus including heterogeneously vancomycin-intermediate S. aureus (hVISA). The gold standard for identification of hVISA is the population analysis profile area under the curve ratio (PAP-AUC), though this method is time-consuming and labour-intensive. The objective of this study was to compare a new method for detection of hVISA, the Etest GRD, to PAP-AUC and to macro Etest. METHODS: One hundred clinical hVISA and 50 clinical fully vancomycin-susceptible S. aureus (VSSA), confirmed by PAP-AUC, were evaluated. Microtitre and Etest MICs were determined by standard testing procedures on all isolates. Macro Etest was performed according to referenced procedures. The Etest GRD was tested using a 0.5 McFarland standard on Mueller-Hinton agar + 5% blood and read at 24 and 48 h. If either the vancomycin or the teicoplanin end of the GRD strip was >or=8 and the vancomycin Etest was

Characterization of vancomycin-heteroresistant Staphylococcus aureus from the metropolitan area of Detroit, Michigan, over a 22-year period (1986 to 2007).

We screened for heteroresistant, vancomycin-intermediate Staphylococcus aureus (hVISA) among clinical isolates of methicillin-resistant S. aureus collected from three hospitals (two urban teaching hospitals and one community hospital) in the Detroit metropolitan area over a 22-year period. The Macro Etest method was used to screen all available isolates. Confirmation of hVISA-positive screens were confirmed by population-area under the concentration-time curve (AUC) analysis. A total of 1,499 isolates revealed hVISA/VISA rates of 2.2/0.4% (n = 225; 1986 to 1993), 7.6/2.3% (n = 356; 1994 to 2002), and 8.3/0.3% (n = 917; 2003 to 2007). Population-AUC analysis confirmed 92.6% of the hVISA-positive strains determined by the Macro Etest method. For the isolates with known sources (1,208), the predominant source of hVISA was blood (60%), followed by lung (21%), skin and wound infections (14%), abscess (1%), and other (4%). The percentage of hVISA-positive strains appeared to increase as a function of the vancomycin MIC. Staphylococcal cassette chromosome mec (SCCmec) typing revealed that the majority (56.9%) of the hVISA strains were SCCmec type II and 39.4% were type IV; the majority of these strains were collected from 2000 to 2007. Our data indicate that the prevalence of hVISA may be increasing. Based on the association of vancomycin treatment failure in patients with hVISA, surveillance of hVISA strains is warranted.

Synthesis and antibacterial properties of (-)-nor-platencin.

An asymmetric Diels-Alder reaction between acrolein and 1-benzyloxymethyl-1,3-cyclohexadiene affords a bicyclic aldehyde that was elaborated in 11 steps to nor-platencin. nor-Platencin is 4-16 times less active than platencin against several resistant strains of Staphylococcus aureus, macrolide-resistant Enterococcus faecalis, and vancomycin-resistant Enterococcus faecium.